Abstract
ABSTRACT Objectives Cyclodextrins (CDs) play a pivotal role in the controlled release of drugs; however, their ability to gradually release drugs is here interrogated: can cyclodextrins, even those that form strong inclusion complexes, sustain a prolonged release of drugs? Methods An original chromatographic approach was developed and accordingly we classified and determined drugs that form the most stable inclusion complexes with cyclodextrins. β-CD and hydroxypropyl-β-CD (HP-β-CD) were coupled to pullulan (Pul) microspheres and packed into a chromatographic column. Then, different drugs or model compounds were eluted, and values of the retention time (RT) were determined. In vitro release studies were performed for drugs that form the most stable inclusion complexes. Results The drugs with the longest RT value form the most stable inclusion complexes with Pul/β-CD and Pul/HP-β-CD microspheres. Pul/β-CD microspheres form more stable inclusion complexes than Pul/HP-β-CD microspheres. However, in spite of their high stability, they were not able to gradually release the included drug (15 min release time). The cross-chromatographic experiments confirmed the hypothesis that in aqueous solution, drug/cyclodextrin complexes are continuously associated and dissociated. Conclusions If the dissociation of the guest molecule is very rapid, why is it expected that these complexes gradually release the drug?
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